The present invention relates to selective neuropeptide Y Y5 receptor antagonists useful in the treatment of eating disorders and diabetes, pharmaceutical compositions containing the compounds, and methods of treatment using the compounds.
Neuropeptide Y is a 36 amino acid peptide that is widely distributed in the central and peripheral nervous systems. This peptide mediates a number of physiological effects through its various receptor subtypes. Studies in animals have shown that neuropeptide Y is a powerful stimulus of food intake, and it has been demonstrated that activation of neuropeptide Y Y5 receptors results in hyperphagia and decreased thermogenesis. Therefore compounds that antagonize neuropeptide Y at the Y5 receptor subtype represent an approach to the treatment of eating disorders such as obesity and hyperphagia.
Phenyl amides and ureas are known as antiatherosclerotic agents, see for example U.S. Pat. No. 4,623,662, and benzoic acid amides are disclosed as antidiabetic agents in U.S. Pat. No. 5,378,728. N,N-alkylenebis-(benzamides) are known as endocrinological agents, see U.S. Pat. No. 4,009,208. WO 98/35957, published Aug. 20, 1998, discloses amide derivatives as selective neuropeptide Y receptor antagonists.